The Skeletal Biology Unit has focused on bone marrow stromal cells (BMSCs), which have the ability to form bone, cartilage, hematopoiesis-supportive stroma, associated fat cells, and perhaps other connective tissues as well, and are important mediators of skeletal metabolism in the post-natal organism. Previously, we had found that some, but not all, of the members of the stromal cell population maintain their ability to form bone, hematopoiesis supportive stroma and associated adipocytes. The differences between non-bone forming clones, clones that form bone are being further investigated by examining their expression of receptors, growth factors, extracellular matrix proteins and transcription factors and other phenotypic markers. These studies are being performed using in vitro analysis of phentypic by using RT-PCR and microarray analysis, and by in vivo transplantation. In collaboration with investigators at the University of North Carolina, we have used a new approach, to isolate and characterize human cementoblasts for the first time. These cells were found to be similar, but not identical to cells that produce bone. This provides an excellent model system to study the physiology of this unusual cell type, and for future design of periodontal reconstructions. The program has continued its collaboration with members of NHGRI in the Skeletal Genome Anatomy Project (SGAP) which is designed to aide in gene discovery and to determine changes in the pattern of gene expression of skeletally derived cells as a function of developmental age and of disease processes. To date, over 10,000 clones from two of our libraries have been sequenced and are being analyzed for novel and unknown gene expression, and the pattern of gene expression within two different libraries is being compared. Bone-enhance arrays are being developed for these studies.